Advanced Solid TumorPhase 1NCT06509906
M9466 in Combination With Topoisomerase 1 Inhibitors-based Regimens in Advanced Solid Tumors and Colorectal Cancer (DDRiver 511)
A Phase 1 study testing M9466, Irinotecan and Folinic acid in people with Advanced Solid Tumor, run by EMD Serono Research & Development Institute, Inc. at 12 sites in 5 countries.
Trial summary
The purpose of this study is to evaluate the safety and preliminary clinical activity of M9466 in combination with topoisomerase 1 inhibitors-based regimens. As such the combination with FOLFIRI (folinic acid, fluorouracil, irinotecan) and Bevacizumab will be evaluated in participants with colorectal cancer, to… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- M9466, Irinotecan and Folinic acid
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 12 sitesin 5 countries
- Study dates
- 8 Oct 2024to 2 Dec 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- M9466 + Irinotecan Run-in Cohort: Participants with locally advanced or metastatic disease that is refractory to standard therapy or for which no standard therapy is judged appropriate by the Investigator (that is [i.e.] participants who have exhausted all standard of care (SoC) options according to International Guidelines), and who may derive clinical benefit from the combination treatment with M9466 and irinotecan
- M9466 + FOLFIRI + Bevacizumab Dose Finding Cohorts: Participants with documented histopathological diagnosis of locally advanced or metastatic colorectal cancer (CRC), who were intolerant/refractory to or progressed after standard systemic therapies for the advanced/metastatic stage that included: Oxaliplatin and a fluoropyrimidine (administration in the adjuvant setting fulfills this criterion if progression occurred within 12 months of the last dose). Prior use of irinotecan is permitted; Either an anti- epidermal growth factor receptor (anti-EGFR) or an anti- Vascular endothelial growth factor (anti-VEGF) agent (not applicable if oxaliplatin was administered in the adjuvant setting); An immune checkpoint inhibitor for participants with known MSI-H status; Anti-EGFR agent and BRAF tyrosine kinase inhibitor ± MEK inhibitor, if locally available, for participants with BRAF V600E mutations. Participants may have received maximally 1 previous regimen for the treatment of metastatic disease (with the exception of participants with MSI-H disease or BRAF positive disease who are allowed to have had up to 2 previous lines of treatment)
- Eastern Cooperative Oncology Group performance status (ECOG PS) less than or equal to (<=) 1
- Other protocol defined inclusion criteria could apply
Who cannot join
- Persistence of AEs related to any prior treatments that have not recovered to Grade <= 1 by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0) unless AEs are clinically nonsignificant and/or stable on supportive therapy in the opinion of the Investigator (for example [e.g.] neuropathy or alopecia)
- History of additional malignancy within 3 years before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, benign prostate neoplasm/hypertrophy, or malignancy that in the opinion of the Investigator, is considered cured with minimal risk of recurrence within 3 years). Participants with history of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) are excluded, irrespective of timeframe
- Participant with known polymorphisms in UGT1A1, DPYD or other enzymes known to predict for increased toxicity from irinotecan or 5 fluorouracil (5-FU) should be excluded; if status is unknown testing is not mandated, unless required by local guidance. Participants that discontinued prior 5-FU treatment due to toxicity are also excluded
- Participants with known brain metastases, except if clinically controlled, which is defined as individuals with central nervous system (CNS) tumors that have been treated and are asymptomatic, and who have discontinued steroids (for the treatment of CNS tumors) for > 28 days prior to first dose of study intervention
- Other protocol defined exclusion criteria could apply
Trial locations and contacts
12 sites in 5 countries.
12 sites in 5 countries
United States4 sites
Sarah Cannon Research Institute at Health One
Denver, Colorado, 80218
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030-4009
Vanderbilt University - 150912667
Nashville, Tennessee, 37232
Carolina BioOncology Institute, LLC - Cancer Therapy and Research Center
Pennington, New Jersey, 08534
Australia3 sites
Cancer Research SA
Elizabeth Vale
St George Private Hospital
Kogarah
Peter MacCallum Cancer Centre - Use the one with Account 2 VCCC
Parkville
South Korea2 sites
Samsung Medical Center
Seoul
Seoul National University Hospital
Seoul
Spain2 sites
NEXT Barcelona - NEXT Barcelona
Barcelona
NEXT Madrid - Hospital Universitario Quironsalud Madrid
Pozuelo de Alarcón
About this study
Official title: An Open Label, Multicenter, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of the PARP1 Inhibitor M9466 in Combination With Topoisomerase 1 Inhibitor-based Regimens in Advanced Solid Tumors and Colorectal Cancer (DDRiver 511)
The purpose of this study is to evaluate the safety and preliminary clinical activity of M9466 in combination with topoisomerase 1 inhibitors-based regimens. As such the combination with FOLFIRI (folinic acid, fluorouracil, irinotecan) and Bevacizumab will be evaluated in participants with colorectal cancer, to establish the M9466 maximum tolerated dose if observed and the recommended dose for expansion.
Study Duration: After a Screening period of up to 28 days, enrolled participants will remain in the study until they have completed all the study visits or until they withdraw consent, are lost to follow-up, or die.
Visit Frequency: The participants will come for a Screening Visit and 1 to 2 visits per treatment cycle. After end of study intervention period, the participants will come for an End of Treatment Visit and a Safety Follow-up Visit.
- Conditions
- Advanced Solid Tumor
- Being tested
- M9466, Irinotecan, Folinic acid, Fluorouracil (5-FU), Bevacizumab
- Keywords
- PARP inhibitor, DNA repair inhibitor, Irinotecan, FOLFIRI
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
M9466Drug
Also called HRS-1167
M9466 will be administered orally until progressive disease, unacceptable toxicity, death, or end of study.
IrinotecanDrug
Irinotecan will be administered intravenously once every 2 weeks (q2w) until progressive disease, unacceptable toxicity, death, or end of study.
Folinic acidDrug
Also called Calcium folinate Leucovorin
Folinic acid will be administered intravenously q2w as per standard of care.
Fluorouracil (5-FU)Drug
Also called 5-FU
Fluorouracil will be administered intravenously as per standard of care.
BevacizumabDrug
Bevacizumab will be administered intravenously, q2w until progressive disease, unacceptable toxicity, death, or end of study.
Granulocyte colony stimulating factor (G-CSF)Drug
G-CSF will be administered subcutaneously at every cycle of study intervention as per standard of care.
| Study group | Role | What they receive |
|---|---|---|
| M9466 + Irinotecan (Run-in Cohort) | Experimental | Not described Receives: Drug: M9466; Drug: Irinotecan; Drug: Granulocyte colony stimulating factor (G-CSF) |
| M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts) | Experimental | Not described Receives: Drug: M9466; Drug: Irinotecan; Drug: Folinic acid; Drug: Fluorouracil (5-FU); Drug: Bevacizumab; Drug: Granulocyte colony stimulating factor (G-CSF) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Treatment Related TEAEs
Measured: Time from signing Informed Consent Form (ICF) up to 30 days after end of study intervention (approximately assessed up to 18.7 months)
Number of Participants with Dose Limiting Toxicity (DLT)
Measured: Day 1 up to Day 28 of the first two Cycles (each cycle is of 14 days)
Secondary outcomes (2)
Pharmacokinetic (PK) Plasma Concentration of M9466
Measured: Pre-dose up to 6 hours post-dose on Cycle 1 Day 1; (each cycle is of 14 days)
Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) Assessed by Investigator
Measured: Time from first treatment of study intervention up to planned assessment at 18.7 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Jul 2024
- Study start8 Oct 2024
- Primary completion2 Dec 2025
- Study completion2 Dec 2025
Why it stopped: Sponsor Decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- More trials run by EMD Serono Research & Development Institute, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Responsible party
- Sponsor
- Investigators
- Medical Responsible, Study director, EMD Serono Research & Development Institute, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06509906
- Sponsor's protocol ID
- MS202650_0001
- Other IDs
- 2024-514155-15-00
- Status last verified
- Dec 2025
- First submitted
- 15 Jul 2024
- Last updated
- 18 Dec 2025
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label, Multicenter, Phase 1 Study to Evaluate the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of the PARP1 Inhibitor M9466 in Combination With Topoisomerase 1 Inhibitor-based Regimens in Advanced Solid Tumors and Colorectal Cancer (DDRiver 511)
- ClinicalTrials.gov ID
- NCT06509906
- Acronym / sponsor ID
- MS202650_0001
- Conditions
- Advanced Solid Tumor
- Keywords
- PARP inhibitor, DNA repair inhibitor, Irinotecan, FOLFIRI
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Decision
- Enrolment
- 3 participants (actual)
- Lead sponsor
- EMD Serono Research & Development Institute, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Merck KGaA, Darmstadt, Germany
- Study start
- 8 Oct 2024 (actual)
- Primary completion
- 2 Dec 2025 (actual)
- Study completion
- 2 Dec 2025 (actual)
- First posted
- 19 Jul 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to evaluate the safety and preliminary clinical activity of M9466 in combination with topoisomerase 1 inhibitors-based regimens. As such the combination with FOLFIRI (folinic acid, fluorouracil, irinotecan) and Bevacizumab will be evaluated in participants with colorectal cancer, to establish the M9466 maximum tolerated dose if observed and the recommended dose for expansion.
Study Duration: After a Screening period of up to 28 days, enrolled participants will remain in the study until they have completed all the study visits or until they withdraw consent, are lost to follow-up, or die.
Visit Frequency: The participants will come for a Screening Visit and 1 to 2 visits per treatment cycle. After end of study intervention period, the participants will come for an End of Treatment Visit and a Safety Follow-up Visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| M9466 + Irinotecan (Run-in Cohort) | Experimental | Drug: M9466, Drug: Irinotecan, Drug: Granulocyte colony stimulating factor (G-CSF) |
| M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts) | Experimental | Drug: M9466, Drug: Irinotecan, Drug: Folinic acid, Drug: Fluorouracil (5-FU), Drug: Bevacizumab, Drug: Granulocyte colony stimulating factor (G-CSF) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- M9466 + Irinotecan Run-in Cohort: Participants with locally advanced or metastatic disease that is refractory to standard therapy or for which no standard therapy is judged appropriate by the Investigator (that is [i.e.] participants who have exhausted all standard of care (SoC) options according to International Guidelines), and who may derive clinical benefit from the combination treatment with M9466 and irinotecan
- M9466 + FOLFIRI + Bevacizumab Dose Finding Cohorts: Participants with documented histopathological diagnosis of locally advanced or metastatic colorectal cancer (CRC), who were intolerant/refractory to or progressed after standard systemic therapies for the advanced/metastatic stage that included: Oxaliplatin and a fluoropyrimidine (administration in the adjuvant setting fulfills this criterion if progression occurred within 12 months of the last dose). Prior use of irinotecan is permitted; Either an anti- epidermal growth factor receptor (anti-EGFR) or an anti- Vascular endothelial growth factor (anti-VEGF) agent (not applicable if oxaliplatin was administered in the adjuvant setting); An immune checkpoint inhibitor for participants with known MSI-H status; Anti-EGFR agent and BRAF tyrosine kinase inhibitor ± MEK inhibitor, if locally available, for participants with BRAF V600E mutations. Participants may have received maximally 1 previous regimen for the treatment of metastatic disease (with the exception of participants with MSI-H disease or BRAF positive disease who are allowed to have had up to 2 previous lines of treatment)
- Eastern Cooperative Oncology Group performance status (ECOG PS) less than or equal to (<=) 1
- Other protocol defined inclusion criteria could apply
Key exclusion criteria (5 listed)
- Persistence of AEs related to any prior treatments that have not recovered to Grade <= 1 by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI-CTCAE v5.0) unless AEs are clinically nonsignificant and/or stable on supportive therapy in the opinion of the Investigator (for example [e.g.] neuropathy or alopecia)
- History of additional malignancy within 3 years before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, benign prostate neoplasm/hypertrophy, or malignancy that in the opinion of the Investigator, is considered cured with minimal risk of recurrence within 3 years). Participants with history of myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) are excluded, irrespective of timeframe
- Participant with known polymorphisms in UGT1A1, DPYD or other enzymes known to predict for increased toxicity from irinotecan or 5 fluorouracil (5-FU) should be excluded; if status is unknown testing is not mandated, unless required by local guidance. Participants that discontinued prior 5-FU treatment due to toxicity are also excluded
- Participants with known brain metastases, except if clinically controlled, which is defined as individuals with central nervous system (CNS) tumors that have been treated and are asymptomatic, and who have discontinued steroids (for the treatment of CNS tumors) for > 28 days prior to first dose of study intervention
- Other protocol defined exclusion criteria could apply
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| M9466Also: HRS-1167M9466 will be administered orally until progressive disease, unacceptable toxicity, death, or end of study. | Drug | M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts), M9466 + Irinotecan (Run-in Cohort) |
| IrinotecanIrinotecan will be administered intravenously once every 2 weeks (q2w) until progressive disease, unacceptable toxicity, death, or end of study. | Drug | M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts), M9466 + Irinotecan (Run-in Cohort) |
| Folinic acidAlso: Calcium folinate LeucovorinFolinic acid will be administered intravenously q2w as per standard of care. | Drug | M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts) |
| Fluorouracil (5-FU)Also: 5-FUFluorouracil will be administered intravenously as per standard of care. | Drug | M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts) |
| BevacizumabBevacizumab will be administered intravenously, q2w until progressive disease, unacceptable toxicity, death, or end of study. | Drug | M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts) |
| Granulocyte colony stimulating factor (G-CSF)G-CSF will be administered subcutaneously at every cycle of study intervention as per standard of care. | Drug | M9466 + FOLFIRI (folinic acid, fluorouracil, irinotecan) + Bevacizumab (Dose Finding Cohorts), M9466 + Irinotecan (Run-in Cohort) |
Primary outcome
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Treatment Related TEAEs
Time frame: Time from signing Informed Consent Form (ICF) up to 30 days after end of study intervention (approximately assessed up to 18.7 months)
Number of Participants with Dose Limiting Toxicity (DLT)
Time frame: Day 1 up to Day 28 of the first two Cycles (each cycle is of 14 days)
2 secondary outcomes
Pharmacokinetic (PK) Plasma Concentration of M9466
Time frame: Pre-dose up to 6 hours post-dose on Cycle 1 Day 1; (each cycle is of 14 days)
Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) Assessed by Investigator
Time frame: Time from first treatment of study intervention up to planned assessment at 18.7 months
Results and safety
The study was stopped early (reason given: Sponsor Decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Dec 2025.
- Trial Awareness and Transparency websiteLink provided by the sponsor.
- US Medical Information website, Medical ResourcesLink provided by the sponsor.
- Individual participant dataSharing planned: No. We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Responsible study director
EMD Serono Research & Development Institute, Inc.
12 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing M9466, Irinotecan and Folinic acid in people with Advanced Solid Tumor, run by EMD Serono Research & Development Institute, Inc. at 12 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Dec 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in United States, Australia, South Korea, Spain, Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor Decision). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Treatment Related TEAEs (time frame: Time from signing Informed Consent Form (ICF) up to 30 days after end of study intervention (approximately assessed up to 18.7 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Dec 2025.